Yes‐Associated Protein is up‐regulated by mechanical overload and is sufficient to induce skeletal muscle hypertrophy
Open accessAbstract
Mechanically‐induced skeletal muscle growth is regulated by mammalian/mechanistic target of rapamycin complex 1 (mTORC1). Yes‐Associated Protein (YAP) is a mechanically‐sensitive, and growth‐related, transcriptional co‐activator that can regulate mTORC1. Here we show that, in skeletal muscle, mechanical overload promotes an increase in YAP expression; however, the time course of YAP expression is markedly different from that of mTORC1 activation. We also show that the overexpression of YAP induces hypertrophy via an mTORC1‐independent mechanism. Finally, we provide preliminary evidence of possible mediators of YAP‐induced hypertrophy (e.g. increased MyoD and c‐Myc expression, and decreased Smad2/3 activity and muscle ring finger 1 (MuRF1) expression).
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Yap in muscle fibres promotes skeletal muscle hypertrophy.
“whereas Yap in 45 muscle fibres and cardiomyocytes promotes skeletal muscle hypertrophy and cardiomyocyte 46 adaptations, respectively.”
From The Hippo signal transduction network for exercise physiologists (2016) · cites this paper as [46]
Increased Yap activity can promote muscle hypertrophy.
“Given that increased Yap activity can promote muscle hypertrophy (46, 148)”
From The Hippo signal transduction network for exercise physiologists (2016) · cites this paper as [46]
Overexpression of Yap in mouse tibialis anterior muscle reduced the activity of a Smad binding element reporter by approximately 85%.
“In line with this, the overexpression of Yap in mouse tibialis anterior muscle reduced the activity of a Smad binding element (SBE) reporter by approximately 85% (46).”
From The Hippo signal transduction network for exercise physiologists (2016) · cites this paper as [46]
Fibres overexpressing YAP were larger than control fibres, demonstrating that elevated YAP activity can cause hypertrophy.
“The fibres overexpressing YAP were larger than control fibres, demonstrating that elevated YAP activity could cause hypertrophy ( Table 1 ).”
From The Hippo signal transduction network for exercise physiologists (2016) · cites this paper as [46]
YAP induced MyoD and Myc reporters while inhibiting a Smad binding element (CAGA)-containing reporter.
“Additionally, they found that YAP induced MyoD and Myc reporters, whilst inhibiting a Smad binding element (CAGA)-containing reporter (46).”
From The Hippo signal transduction network for exercise physiologists (2016) · cites this paper as [46]
YAP expression increases up to approximately 4.5-fold in the hypertrophying plantaris muscle after synergist ablation.
“In another study, the Hornberger group reported that YAP expression increases up to approximately 4.5 folds in the hypertrophying plantaris muscle days synergist ablation, a model commonly used to induce skeletal muscle hypertrophy (46).”
From The Hippo signal transduction network for exercise physiologists (2016) · cites this paper as [46]
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References 44 · Cited by 121
- Authors
- Goodman, C. A., Dietz, J. M., Jacobs, B. L., McNally, R. M., You, J.-S., & Hornberger, T. A.
- Affiliations
- University of Wisconsin System (US)
- University of Wisconsin–Madison (US)
- Corresponding author
- Goodman, Craig A.
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 2015-05-08
- Volume
- 589
- Issue
- 13
- Pages
- 1491-1497
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- PMC
- PMC4442043
- OpenAlex
- W1825669598
- Cited by
- 121
- References
- 44
- Citations by year
- 2026: 9 · 2025: 7 · 2024: 14 · 2023: 16 · 2022: 11 · 2021: 19 · 2020: 7 · 2019: 10 · 2018: 9 · 2017: 5 · 2016: 10 · 2015: 2
- FWCI
- 4.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Victoria University Research Repository (Victoria University) (submittedVersion)
- Funders
- National Institutes of Health (AR057347, AR063256)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Keywords
- YAP, mechanical overload, skeletal muscle hypertrophy, mTORC1, mechanotransduction, MyoD, c-Myc, Smad2/3, MuRF1, muscle growth
- MeSH terms
- Tripartite Motif Proteins, Mechanistic Target of Rapamycin Complex 1, YAP-Signaling Proteins, Animals, Female, Gene Expression Regulation, Hypertrophy, Male, Microscopy, Fluorescence, Muscle Proteins, Phosphoproteins, Promoter Regions, Genetic, Stress, Mechanical, Blotting, Western, Signal Transduction, Up-Regulation, Proto-Oncogene Proteins c-myc, MyoD Protein, Muscle, Skeletal, Cell Cycle Proteins, Ubiquitin-Protein Ligases, Multiprotein Complexes, Adaptor Proteins, Signal Transducing, Mice, Smad2 Protein, Smad3 Protein, TOR Serine-Threonine Kinases
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